A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity

Orla Howe*, Lisa White, Daniel Cullen, Grainne O’brien, Laura Shields, Jane Bryant, Emma Noone, Shirley Bradshaw, Marie Finn, Mary Dunne, Aoife M. Shannon, John Armstrong, Brendan McClean, Aidan Meade, Christophe Badie, Fiona M. Lyng

*Corresponding author for this work

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Abstract

The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4‐gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation‐responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation‐induced G2 chromosomal radio-sensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4‐ gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation‐induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors high-lighting intra‐individual heterogeneity of prostate cancer donors.

Original languageEnglish
Article number10607
JournalInternational Journal of Molecular Sciences
Volume22
Issue number19
DOIs
Publication statusPublished - 30 Sep 2021

Bibliographical note

Funding Information: This research was funded by EU FP7 Network of Excellence DoReMi (Grant Number 249689) and Science Foundation Ireland (11/RFP.1/BMT/3317).

Open Access: This article is an open access article distributed under the terms and conditions of the Creative Commons
Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Citation: Howe, O.; White, L.; Cullen, D.; O’Brien, G.; Shields, L.; Bryant, J.; Noone, E.; Bradshaw, S.; Finn, M.; Dunne, M.; et al. A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity. Int. J. Mol. Sci. 2021, 22, 10607.

DOI: https://doi.org/10.3390/ijms221910607

Keywords

  • Biomarkers
  • Gene expression
  • radiosensitivity

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